Early treatment failure during treatment of Plasmodium falciparum malaria with atovaquone-proguanil in the Republic of Ivory Coast (original) (raw)
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Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance. This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information. Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carryin...
Failure of atovaquone-proguanil malaria chemoprophylaxis in a traveler to Ghana
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Clinical failure of Malarone™ chemoprophylaxis is extremely rare. We report a case of Plasmodium falciparum malaria in a returned traveler to Ghana who fully adhered to atovaquone-proguanil (Malarone™) chemoprophylaxis daily dosing, yet took the pills on an empty stomach. Screening of the P. falciparum isolate revealed triple codon mutation of Dhfr at positions 51, 59, and 108. Plasma drug levels of both atovaquone and proguanil revealed sub-therapeutic concentrations.
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The American journal of tropical medicine and hygiene, 2007
The fixed dose combination of atovaquone and proguanil hydrochloride, marketed under the trade name Malarone, is the most recently approved agent in North America for the prevention and treatment of chloroquine- and multi-drug resistant Plasmodium falciparum malaria. In both adult and pediatric populations, atovaquone-proguanil demonstrates consistently high protective efficacy against P. falciparum, and in treatment trials, cure rates exceed 93%. Only a handful of genetically confirmed treatment failures have been reported to date. Atovaquone-proguanil has an excellent safety profile during both prophylaxis and treatment courses, with severe adverse events rarely reported. This topical review will examine the evidence behind the current indications for use of atovaquone-proguanil, and will summarize the current body of literature surrounding safety and tolerability.
Malaria journal, 2002
We report the first in vitro and genetic confirmation of Malarone (GlaxoSmithKline; atovaquone and proguanil hydrochloride) resistance in Plasmodium falciparum acquired in Africa. On presenting with malaria two weeks after returning from a 4-week visit to Lagos, Nigeria without prophylaxis, a male patient was given a standard 3-day treatment course of Malarone. Twenty-eight days later the parasitaemia recrudesced. Parasites were cultured from the blood and the isolate (NGATV01) was shown to be resistant to atovaquone and the antifolate pyrimethamine. The cytochrome b gene of isolate NGATV01 showed a single mutation, Tyr268Asn which has not been seen previously.
Plasmodium falciparum Malaria and Atovaquone-Proguanil Treatment Failure
Emerging Infectious Diseases, 2008
We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum-infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened.
Journal of Travel Medicine, 2006
Background: Previous experience with unacceptable adverse effects with mefloquine as treatment for uncomplicated Plasmodium falciparum malaria prompted an evaluation of the effectiveness and side effects of atovaquone-proguanil (Malarone) in a hospital setting. Methods: Atovaquone-proguanil was given as standard treatment (1,000/400 mg q.d. for 3 days) to 50 adults who had traveled in Africa and returned with uncomplicated Plasmodium falciparum malaria. Half of the treated patients were African and had lived outside Africa for varying periods of time; the other half were Danish-born persons without any previous immunity towards malaria. Results: All patients treated with Malarone were cured without complications. The mean fever clearance times differed among the groups and according to various degrees of prior exposure to malaria and ranged from 1.3 to 2.2 days. Adverse effects during treatment were mild, and were likely to be due to the malaria itself. Fourteen people who had acquired falciparum malaria in spite of taking proguanil-chloroquine prophylaxis were also cured uneventfully without recrudescence. Conclusions: Malarone appears to be an effective, safe and acceptable oral treatment for uncomplicated malaria.
The American journal of tropical medicine and hygiene, 1999
Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n = 136), or one placebo tablet daily (n = 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P < 0.001). The most commonly reported adverse events with at...
The American journal of tropical medicine and …, 2005
The importation of drug-resistant malaria is a growing public health problem in non-endemic countries. The combination of atovaquone and proguanil (Malarone™) has become established as an agent of choice to prevent and treat chloroquine-resistant Plasmodium falciparum malaria in travelers. We describe the first reported case in North America of genetically confirmed atovaquone/proguanil-resistant P. falciparum malaria. Polymerase chain reaction and sequence analysis of the primary and recrudescent isolates confirmed the acquisition of a point mutation (Tyr268Ser) in the cytochrome b gene of the recrudescent isolate known to confer high-level resistance to atovaquone. Suboptimal therapy may have played a contributory role in the emergence of resistance.